We applied first‐arrival seismic tomography to 3D seismic refraction experimental data observed in the middle‐lower Yangtze River region, Anhui Province, eastern China, in an area by 150 km. This experiment used the seismic energy released by large‐volume airgun shots to image crustal velocity structure. The first‐arrival phases generated by airgun shots can be clearly traced to a distance larger than 160 km after stacking waveforms over 300 repetitive shots at nearly fixed sites. A regularized nonlinear travel‐time inversion algorithm was used to develop a 3D compressional velocity model with smooth minimum structure. A total of 2549 picked first‐arrival travel times with automatically determined uncertainty were inverted. Our final preferred velocity model shows a good correspondence with regional geological units. The model also contains high‐velocity anomalies beneath regional ore deposit fields. Checkerboard resolution tests show that 10 km lateral velocity anomalies can be recovered throughout most of the model. Our study has successfully demonstrated a classic seismic survey using environmentally friendly airgun sources in a land‐based water body for high‐resolution imaging of crustal structures.